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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: Tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder, can lead to the development of hamartomas in various organs, including the heart, lungs, kidneys, skin and brain.

The management of subependymal giant cell tumors (SGCTs) is still controversial, and peri- and/or intraventricular neoplasms may lead to life-threatening hydrocephalus.

The data were collected after a bibliography made using PubMed/Medline with these terms: subependymal, subependymal giant cell astrocytoma, subependymal giant celltumor, and tuberous sclerosis complex.

RESULTS: SGCTs are shown to be generated from a glioneuronal lineage, but their filiation with subependymal nodules (SENs) is still under debate.

CONCLUSIONS: An earlier diagnosis of SGCT in neurologically asymptomatic children with TSC may allow a precocious surgical removal of the tumor before the installation of increased intracranial pressure signs, an attitude that is being progressively adopted to lessen the morbimortality rate.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]Subependymal giant cell astrocytoma with intratumoral hemorrhage in the absence of tuberous sclerosis.

Subependymal giant cell astrocytoma (SEGA) is an uncommon tumor that usually occurs in the setting of tuberous sclerosis (TS) syndrome.

We report a rare case of an intratumoral and a small intraventricular hemorrhage complicating a SEGA in an adult patient without any signs of TS.

Although pre-operative CT and MRI findings for the tumor were typical of SEGA, SEGA was not considered in the differential diagnosis because the patient was lacking any symptoms of TS.

This is the second report of intraventricular and intratumoral hemorrhage complicating a SEGA and the first case in which these complications occurred in an adult patient in whom there was no previous suspicion of systemic disease.

[Title] A case of solitary subependymal giant cell astrocytoma: two somatic hits of TSC2 in the tumor, without evidence of somatic mosaicism.

There are several case reports of solitary SEGA without any other manifestations of TSC.

Here, we report a 20-year-old woman with a brain tumor.

Pathological diagnosis was consistent with SEGA, but comprehensive clinical screening found no other lesions indicative of TSC.

Molecular analysis of the tumor revealed loss of heterozygosity and allelic mutation (5228G>A, R1743Q) of TSC2.

According to these results, this patient should be considered as having SEGA that developed from two somatic hit mutations in TSC2, rather than being a TSC2 patient with a very small fraction of somatic mosaicism.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

BACKGROUND: Neurosurgical resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex.

METHODS: Patients 3 years of age or older with serial growth of subependymal giant-cell astrocytomas were eligible for this open-label study.

The primary efficacy end point was the change in volume of subependymal giant-cell astrocytomas between baseline and 6 months.

Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%).

There were no new lesions, worsening hydrocephalus, evidence of increased intracranial pressure, or necessity for surgical resection or other therapy for subependymal giant-cell astrocytoma.

CONCLUSIONS: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed. (Funded by Novartis; ClinicalTrials.gov number, NCT00411619.).

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Subependymal giant-cell astrocytoma (SEGA) is a rare intra-ventricular low-grade tumor which frequently occurs as a manifestation of tuberous sclerosis complex.

The histogenesis of SEGA is controversial and its astrocytic nature has been doubted.

First studies suggested the astrocytic nature of SEGA while several recent reports demonstrate its glio-neuronal nature.

In spite of this, in the recently revised WHO classification of the CNS tumors, SEGA has been still included in the group of astrocytomas.

Eight patients (89%) had a solitary lesion located in the lateral ventricle close to of the head of the caudate nucleus, the remaining patient (11%) had two tumors, one located close to the head of the left caudate nucleus and the other in the central part of the right lateral ventricle.

In all four there were glial cell processes filled with intermediate filaments.

Our results emphasize the glio-neuronal nature of SEGA.

We suggest moving it into the group of mixed glio-neuronal tumors under the denomination of subependymal giant celltumor.

Conclusively, coexpression of neuronal and glial markers and expression of nestin in CNs, SEGAs and SEs suggested the origin of these tumor cells might be the stem cells being able to differentiate into both neuronal and glial phenotypes.

But CNs might be originated from rather neuronally committed stem cells and SEs from rather glially committed stem cells.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Subependymal giant cell astrocytomas are one of the three major intracranial lesions found in tuberous sclerosis complex.

Subependymal giant cell astrocytomas are typically slow-growing tumors of mixed glioneuronal lineage which can become aggressive and cause obstructive hydrocephalus usually in older children and adolescents.

Neonatal subependymal giant cell astrocytomas are extremely rare, and their natural history and prognosis are poorly understood.

This report investigates an extremely large neonatal subependymal giant cell astrocytoma which was initially identified in utero at 19 weeks of gestation in a high-risk pregnancy with no family history of tuberous sclerosis complex.

However there are several reported cases in which patients with a solitary SEGA had no other stigmata of TSC.

We describe a case of SEGA in a 75-year-old woman representing the oldest patient reported to-date.

Postmortem examination of the brain revealed a single 2.1 x 1.0 x 0.8 cm intraventricular nodule in the lateral ventricle.

Histologically, it was composed of interlacing bundles of spindle-shaped tumor cells with thin delicate processes admixed with relatively large pleomorphic cells with abundant glassy eosinophilic cytoplasm, as seen in a SEGA.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title]Subependymal giant-cell astrocytomas in pediatric tuberous sclerosis disease: when should we operate?

OBJECTIVE: A small percentage of tuberous sclerosis patients will develop a subependymal giant-cell astrocytoma.

METHODS: We retrospectively reviewed 19 patients treated surgically for intraventricular tumors in Foch Hospital and at the Fondation Adolphe de Rothschild in Paris, France, and we analyzed published pediatric reports from 1980 to 2006.

RESULTS: The results from our own population, as well as from other published pediatric series (15 series), indicate that subependymal giant-cell astrocytomas have a good prognosis when a macroscopically total resection has been performed.

In our series, residual lesions tended to enlarge, but residual tumors remaining stable have been reported.

Larger or symptomatic lesions tend to have a higher morbidity.

CONCLUSION: We think that any lesion fulfilling the criteria for a subependymal giant-cell astrocytoma as previously described in the literature (lesion around the foramen of Monro, greater than 5 mm, with incomplete calcifications) should be removed as soon as clear evidence of growth has been confirmed.

Predominant features included hypercellularity, cell clustering, and fibrillarity.

Although common in histologic sections, perivascular palisading/pseudorosettes and spindled astrocytic cells were rarely noted on smears.

CONCLUSION: The cytologic features of SEGA are highly characteristic and thus are of great use in supporting a diagnosis of SEGA and in excluding mimics, primarily gemistocytic astrocytoma and ependymoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

For example, anterograde amnesia associated with damage to the fornix (Sweet et al, 1959), a fibre bundle connecting the hippocampus to the mamillary bodies within the limbic system, is well described following removal of third ventricle colloid cysts (Hodges and Carpenter, 1991; McMackin et al, 1995; Aggleton et al, 2000), suggesting the importance of the fornix as one of the anatomical substrates of the distributed neural network underpinning memory functions (Mesulam, 1990).

This article reports the cognitive impairments associated with left fornix damage which became apparent following surgical removal of a solitary subependymal giant cell astrocytoma.

The object of this paper is to describe the imaging and clinical characteristics of subependymal nodule (SN) - subependymal giant cell astrocytoma (SGCA) complex in tuberous sclerosis and analyze its evolution in order to attempt early detection and the prevention of intracranial hypertension.

We evaluated 22 patients with the pathological diagnosis of SGCA.

The diagnosis was made at a median of 10.1 years old.

Six patients presented visual deficit and in these, the average diameter of the tumor was 31.5 mm, a high value when compared to 18.7 mm in the patients without visual deficit.

The imaging and clinical follow-up of any subependymal lesion close to the foramen of Monro will permit, at a presymptomatic stage, an anticipation of surgical treatment thus reducing intracranial hypertension incidence.

Prospective studies could determine whether the SN-SGCA complex corresponds to the same entity in distinct evolution stages or to two lesions with different growth potential.

In the present review we summarise immunohistochemical findings of two types of studies performed on giant cells aiming at establishing the expression of hamartin and tuberin level and determining the presence of neuron- or astrocyte-specific markers.

We conclude that giant cells in cortical tubers and SEGAs are the same undifferentiated cells that, depending on individual determination, can show neural or glial features.

Of the genes differentially expressed in TSC, 11 were validated by real-time PCR on independent tumor samples and 3 SEGA-derived cultures.

ANXA1, GPNMB, LTF, RND3, S100A11, SFRP4, and NPTX1 genes were likely to be mTOR effector genes in SEGA, as their expression was modulated by an mTOR inhibitor, rapamycin, in SEGA-derived cells.

Inhibition of mTOR signaling affected size of cultured SEGA cells but had no influence on their proliferation, morphology, or migration, whereas inhibition of both mTOR and extracellular signal-regulated kinase signaling pathways led to significant alterations of these processes.

For the first time, we identified genes related to the occurrence of SEGA and regulated by mTOR and demonstrated an effective modulation of SEGA growth by pharmacological inhibition of both mTOR and extracellular signal-regulated kinase signaling pathways, which could represent a novel therapeutic approach.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Gradual formation of an operative corridor by balloon dilation for resection of subependymal giant cell astrocytomas in children with tuberous sclerosis: specialized minimal access technique of balloon dilation.

BACKGROUND: Major sources of morbidity and mortality in patients with tuberous sclerosis who develop subependymal giant cell astrocytomas (SEGAs) relate to tumor growth and resultant hydrocephalus.

We describe a modification of a specialized minimal access resection technique in which an operative corridor is formed with balloon dilation over the course of a week prior to tumor resection.

METHODS: Three patients with tuberous sclerosis who had an enlarging SEGA and concomitant hydrocephalus underwent surgical resection with this modified technique.

A frontal craniotomy was performed and the optimal trajectory for tumor resection was confirmed by image guidance.

After initial insertion of the deflated balloon into the ventricle and removal of the peel-away sheath, inflation of the balloon with a 1-mL saline injection sealed the tract.

One week after the first operation, the balloon was deflated and removed, and the patient underwent tumor resection via the newly formed operative corridor.

CONCLUSIONS: Use of balloon dilation for the gradual formation of an operative corridor eliminated the need for additional retraction during SEGA resection, potentially decreasing injury to the surrounding neural tissue.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Establishing the correct preoperative diagnosis is important to prevent unnecessary surgical intervention.

Our study includes nine cases of benign lateral ventricle tumors including two cases of central neurocytoma, two of subependymal giant cell astrocytoma, two of pilocytic astrocytoma and three of subependymoma treated surgically between 1996 and 2003.

All three types of tumor demonstrated heterogeneous enhancement on MR imaging with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and increased choline (Cho) peak and decreased N-acetyl aspartate (NAA) and creatine (Cre) peaks on (1)H-MRS. (201)Tl-SPECT showed high uptake of (201)Tl without wash out in all cases of central neurocytoma, subependymal giant cell astrocytoma and pilocytic astrocytoma, but no uptake in cases of subependymoma.

Absence of (201)Tl uptake in contrast with enhancement on MR imaging and the (1)H-MRS features of modest elevation of the Cho/Cre ratio, reduction of the NAA peak and presence of lactate/lipid peaks are characteristic features of subependymomas and useful to establish a preoperative diagnosis.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Differentiating SEGAs from subependymal nodules (SENs) before obstruction occurs may improve the morbidity associated with these tumors.

Resection was recommended for symptomatic and neuroimaging evidence of hydrocephalus (41%), tumor growth without evidence of hydrocephalus (33%), and for poorly controlled seizures (25%).

The mean diameter of the tumors at the time of resection was 1.9 cm (range 0.3-4 cm), and no tumor recurred.

Tumor growth and contrast enhancement are the most common signs of progression on neuroimages, and may be seen prior to the development of obstructive hydrocephalus.

CONCLUSIONS: Patients with SENs and SEGAs should undergo follow-up neuroimaging at yearly intervals, and if lesions show signs of progression (contrast enhancement or growth), these intervals should be shortened and consideration given to early resection.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Tuberous sclerosis (TS), autosomal dominant disorder manifested by the formation of usually benign tumors in the brain, heart, kidneys and skin, results from an inactivating mutation in one of two tumor suppressor genes TSC1 or TSC2.

Very recently it has been hypothesized that the pathway triggered by WNT, one of embryonic growth factors involved in cell differentiation and migration, could be disturbed in TS.

In order to test this hypothesis we evaluated samples of four subependymal giant cell astrocytomas (SEGAs), brain tumors developing in the progress of TS.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] The expression of the O-linked N-acetylglucosamine containing epitope H in the gemistocytic, pilocytic and subependymal giant cell astrocytomas.

In this study the expression of the epitope H was investigated in thirty cases of gemistocytic (WHO grade II), pilocytic (WHO grade I), and subependymal giant cell (WHO grade I) astrocytomas using the mAbH with the indirect immunoperoxidase method.

The dense tumor areas composed of elongated pilocytic cells revealed high expression of the epitope H.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Her tuberous sclerosis was diagnosed at the age of 9, when she developed hydrocephalus caused by subependymal giant cell astrocytoma near the foramen of Monro, which was treated by surgical resection and VP shunt placement followed by radiation and chemotherapy.

Brain MR images revealed a 3 cm enhancing mass extending from the left jugular foramen to the cerebellopontine cistern, accompanied by perifocal edema of the brain stem and cerebellar hemisphere.

The tumor was partially removed via suboccipital craniotomy and histologically diagnosed as a schwannoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

INTRODUCTION: The purpose of this study was to analyze the outcome of patients with grade I astrocytomas treated with radiation therapy, specifically looking at the prognostic significance of age, timing of radiation therapy (immediately after surgery or delayed until progression) and tumor location.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] [Intraventricular fibrous tumor: a case report].

Solitary fibrous tumor was first reported in the pleura; however, it has since been reported in many other locations.

To our knowledge, only eight cases of intraventricular solitary fibrous tumor have been reported.

We describe a case of intraventricular solitary fibrous tumor.The imaging characteristics of intraventricular solitary fibrous tumors are nonspecific; the differential diagnosis should include other tumors that can affect the ventricular system such as meningioma, high grade glioma, metastasis, subependymoma, choroid plexus papilloma, ependymoma, subependymal giant cell astrocytoma, and neurocytoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Signaling pathways involved in hereditary syndromes predisposing to the development of nervous system tumors include RAS, WNT, RB1, TP53, and PTCH signaling pathways, which play key roles in gene regulation, apoptosis, and cell proliferation.

We also briefly review two important advances in this area: the treatment of medulloblastomas in patients with mutations in the PTCH1 gene, and the discovery of deregulated mammalian target of rapamycin as a major oncogenic driver molecule in patients with TSC mutations and subependymal giant cell astrocytoma.

SUMMARY: Progress in the understanding of hereditary nervous system tumors is increasingly important for diagnosis and treatment.

[Chemical-registry-number] 0 / Tumor Suppressor Proteins

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Tumours in which loss of heterozygosity is rare, such as subependymal giant-cell astrocytoma, might all share a common feature that mimics loss of heterozygosity either by inactivation of the TSC complex or by direct activation of mammalian target of rapamycin (mTOR) or its downstream targets.

AKT activation is detected only in few samples, whereas ERK is hyperactive in all subependymal giant-cell astrocytomas.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

The GAC mRNA/KGA mRNA expression ratio was as a rule higher in the neoplastic than in control tissues, irrespective of the cell type dominating in the tumor or tumor malignancy.

LGA mRNA expression was relatively very low in cultured astrocytes, and very low to absent in astrocytoma pilocyticum, ependymoma and subependymal giant cell astrocytoma (SEGA), tumors of astrocytic origin.

The results show that low expression of LGA mRNA is a feature common to normal astrocytes and astroglia-derived tumor cells or ependymomas and can be considered as a cell-type, rather than a malignancy marker.

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The T1 SE/MTC sequence was far superior to other methods in detecting white matter lesions (P<0.01).

There was no significant difference between the T1 SE/MTC and T1 SE (before and after Gd injection) sequences in the detection of subependymal nodules; FLAIR sequence showed less sensitivity than the others in identifying the nodules.

CONCLUSION: We demonstrated the importance of appropriate MRI sequences for diagnosis of the most frequent brain lesions in TS.

Gd injection might be useful in detecting SGCA; however, the parameters of size and location are also important for a presumptive diagnosis of these tumors.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

[Title] Structure of AscE and induced burial regions in AscE and AscG upon formation of the chaperone needle-subunit complex of type III secretion system in Aeromonas hydrophila.

In the type III secretion system (T3SS) of Aeromonas hydrophila, the putative needle complex subunit AscF requires both putative chaperones AscE and AscG for formation of a ternary complex to avoid premature assembly.

Here we report the crystal structure of AscE at 2.7 A resolution and the mapping of buried regions of AscE, AscG, and AscF in the AscEG and AscEFG complexes using limited protease digestion.

The N-terminal 13 residues of AscE are buried only upon binding with AscG, but this region is found to be nonessential for the interaction.

AscE functions as a monomer and can be coexpressed with AscG or with both AscG and AscF to form soluble complexes.

The AscE binding region of AscG in the AscEG complex is identified to be within the N-terminal 61 residues of AscG.

The exposed C-terminal substrate-binding region of AscG in the AscEG complex is induced to be buried only upon binding to AscF.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

EXEGESIS: We report a case of TSC diagnosed in a 33-year-old man, without any known family history of phakomatosis, presenting with facial angiofibromas, hypomelanotic macules, a giant-cell astrocytoma and retinal phakomas without any mental impairment or epilepsy.

CONCLUSION: TSC may occur in patients who do not have any family history of phakomatosis because de novo mutations are frequent.

They should lead to brain imaging in search for astrocytoma, subependymal nodules and cortical tubers which number is directly correlated with the risk of seizures and the degree of mental impairment.

This study found no association between the presence of AHCYTOEN, aerA, hlyA, alt, ast, ascV, aexT or ascF-ascG genes in Aeromonas isolates and the development of extra-intestinal infections or bacteremia.

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[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Patients with Type C tuber dominance have more MRI abnormalities such as subependymal giant cell tumors, and were more likely to have an autism spectrum disorder, a history of infantile spasms, and a higher frequency of epileptic seizures, compared to patients who have a dominance in Type B tubers, and especially to those with a Type A dominance.

Neuroimaging data of lateral ventricle gliomas and central neurocytomas diagnosed in one institution were reviewed and compared to the corresponding literature data.

Our data support those of previous studies in that MRI has been found to be superior to CT for a more precise imaging of lateral ventricle gliomas.

Survival data were available in 65 cases, which have confirmed a favourable outcome in most of the patients with subependymoma, subependymal giant cell astrocytoma, central neurocytomas or pilocytic astrocytoma.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

INTRODUCTION: The aims of the present study were to determine the perfusion characteristics of several types of intraventricular tumors and to evaluate the usefulness of dynamic contrast-enhanced MRI in making the differential diagnosis.

METHODS: A total of 28 patients with intraventricular tumors (five meningiomas, five papillomas, three ependymomas, four subependymomas, seven central neurocytomas, two subependymal giant cell astrocytomas and two metastases) underwent conventional and dynamic susceptibility contrast-enhanced MRI.

Cerebral blood volume (CBV) maps were obtained and the relative CBV (rCBV) calculated for each tumor.

In cases of suspected meningioma, papilloma or neurocytoma, low rCBV values (<3) point to a diagnosis of neurocytoma rather than either of the other tumor types.

CONCLUSION: Susceptibility contrast-enhanced MRI can provide additional information on the vascularization of intraventricular cerebral tumors and may help in making the differential diagnosis.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Most of the low-grade gliomas had no detectable loss of heterozygosity (LOH) in any of the 11,562 SNP loci; exceptions were two gangliogliomas (3q and 9p), one astrocytoma (6q), and two subependymal giant cell astrocytomas (16p and 21q).

This may represent a new molecular mechanism underlying tumor progression.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the formation of hamartomas in multiple organs.

Five to 15% of affected individuals display subependymal giant cell astrocytomas, which can lead to substantial neurological and postoperative morbidity due to the production of hydrocephalus, mass effect, and their typical location adjacent to the foramen of Monro.

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Insomnia is a disorder that affects a large part of the population.

Agents that are used to treat this sleep disorder have evolved: benzodiazepines replaced barbiturates, but there is still concern about their residual effects and about the development of dependence and the risk of withdrawal symptoms.

This article summarises these subjects as well as the pharmacology of investigational drugs, such as indiplon (another benzodiazepine receptor agonist), gaboxadol ( a selective extrasynaptic GABAA agonist -SEGA-), and some anticonvulsant drugs that could be useful as hypnotics: tiagabine ( a GABA transporter inhibitor), pregabaline and gabapentine (GABA analogs).

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[Number-of-references] 15

[Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.

Gaboxadol, an investigational treatment and a selective extrasynaptic GABA(A) receptor agonist (SEGA), targets GABA(A) receptors containing a delta subunit, which are located outside the synaptic junctions of thalamic and cortical neurons thought to play an important regulatory role in the onset, maintenance, and depth of the sleep process.

Eighty percent of small cell glioblstomas were completely negative, but 20% showed heterogeneous positivity for gal-3.

Focal positivity for gal-3 was also found in dysembryoplastic neuroepithelial tumors (DNTs) and gangliogliomas, in which the positive cells were the astrocytic component.

On the basis of our immunohistochemical data in conjunction with previous reports, we therefore conclude that gal-3 is differentially expressed in various brain tumors, and thereby, is a helpful biomarker in making differential diagnoses, especially in cases where a morphological diagnosis is controversial.

After rapid growth for 1 year after its discovery, the optic nerve tumor demonstrated modest progression.

Although her left ventricular subependymal giant celltumor demonstrated a 49% reduction in volume, the optic nerve tumor did not respond, and even underwent slight (6%) growth during the 16-month treatment.

The quality of this child's vision has remained normal in both eyes, and she is otherwise asymptomatic with regard to the optic nerve tumor.